Our long range goal is to elucidate the mechanisms by which glucocorticoids potentiate the bronchial smooth muscle relaxation effects of beta-adrenergic agents because of the importance of this in bronchial asthma therapy. The unifying concept of our research is the idea that steroid hormones regulate tissue sensitivity to beta-adrenergic agonists by altering cyclic AMP responses. One of our working hypotheses is that glucocorticoids alter the properties of adenyl cyclase or beta-receptors in such a way that a given level of beta-adrenergic stimulation produces a greater rate of cyclic AMP synthesis than in glucocorticoid-deficient tissues. Experimental parameters to be measured include: smooth muscle tension, cyclic AMP, adenyl cyclase, cyclic nucleotide phosphodiesterase, protein kinase, binding of beta-adrenergic agonist and/or antagonist and glycogen phosphorylase. Typical protocols will be to prepare (in vivo and in vitro) steroid-pretreated and control tissues and then assess acute effects of beta-agonists. The latter will be assessed both in vivo, in isolated, intact smooth muscle and in cell free extracts depending on the particular experiment. Primary preparations to be used are control and glucocorticoid-pretreated tracheae and control and estrogen-treated uteri. Each has its own advantages and disadvantages and the strategy is to use both preparations cooperatively to elucidate basic mechanisms.